Dramatic increases in survival of high risk neonates have occurred in the last decade. Each year a quarter of a million low birth weight infants are born in the U.S. Most of these infants now survive from intensive care nurseries. Nutritional support for these high risk infants is now the major concern of neonatologists, and mineral nutrient support is the major nutritional concern. The purpose of the present study is to determine the mechanisms of skeletal mineralization in infancy in relation to provision and availability of calcium, phosphorus and vitamin D with two modes of nutrient support commonly used in high risk neonates: parenteral nutrition (PN) and human milk feeding. In Part I the specific purpose is to determine the effect of high versus usual calcium and phosphorus content in infusates on bone mineral content and on serum Ca, P and calciotropic agent concentrations. We propose to test the hypothesis that high Ca and P content with low doses of vit. D in parenteral nutrition solutions will result in increased bone mineral content (BMC) in infants when compared to those on usual Ca and P content in parenteral nutrition fluids with similar doses of vit. D. We hypothesize that preterm infants receiving the high parenteral nutrition regimen will have BMC that approaches BMC in utero, and term infants receiving the high regimen will have BMC that resembles normal infants on human milk; furthermore, high Ca and P supplementation with low vit. D will not result in serum abnormalities of Ca and P. Fifty infants will be studied in a prospective randomized trial. The infants will be matched for weight and gastrointestinal abnormalities. Physical examination and serum Ca, P, magnesium, alkaline phosphatase and bone GLA-protein, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, D binding protein, parathyroid hormone, and calcitonin will be measured. BMC by infant adapted photon absorptiometry and x-ray studies for detection of rickets will be performed. In Part II the purpose is to test the hypothesis that rickets and osteopenia occurs in very low birth weight infants fed human milk even with supplementation with vit. D and that rickets and osteopenia in such infants can be prevented by supplementing with Ca and P. A prospective randomized trial will be performed in 50 infants with birth weights less than 1500 gm. matched for sex, race and weight. Clinical and laboratory investigations will be similar to Part I. Supplemented group will be compared with unsupplemented for rate of rickets, bone demineralization and abnormalities in serum Ca, P and Ca regulatory agents. From these studies, an improved understanding of mechanisms involved in bone mineralization in high risk infants will be obtained and provide a means of assessing Ca regulatory mechanisms in such infants.